Microwave-assisted synthesis and bioevaluation of new sulfonamides

Figures & data

Scheme 1. Synthesis of sulfonamides 8–14 via microwave irradiation.

Table 1. Cytotoxicities of sulfonamides 8–14 toward human oral squamous cell carcinoma cells and human normal oral cells.

CC50 (μM)
	Human oral squamous cell carcinoma cells														Human normal oral cells								TS
Comp.	(A) Ca9-22	SD	SI	HSC-2	SD	SI	HSC-3	SD	SI	HSC-4	SD	SI	(B) Mean CC50	SD	(C) HGF	SD	HPLF	SD	HPC	SD	(D) Mean	SD	(D/B)	(C/A)	PSE(D/B^2) × 100	Log P
8	42.0	5.0	1.8	67.0	12.2	1.1	66.3	11.9	1.1	50.3	7.1	1.5	56.4	12.3	85.0	13.5	54.3	5.0	88.3	6.8	75.9	18.7	1.3	2.0	2.3	1.17
9	25.7	4.2	1.7	33.3	2.1	1.3	39.7	0.6	1.1	31.7	2.1	1.4	32.6	5.8	43.7	4.0	39.3	4.2	49.7	3.8	44.2	5.2	1.4	1.7	4.2	1.63
10	37.7	1.5	1.3	65.3	5.7	0.8	47.0	8.7	1.1	40.7	2.1	1.2	47.7	12.4	47.3	1.5	44.0	2.0	61.0	12.5	50.8	9.0	1.1	1.3	2.2	1.08
11	36.3	2.5	1.6	46.3	10.1	1.3	43.3	5.9	1.4	39.3	4.7	1.5	41.3	4.4	66.7	3.5	43.0	4.6	67.7	0.6	59.1	14.0	1.4	1.8	3.5	1.22
12	22.3	1.5	2.0	39.0	2.6	1.1	38.3	2.5	1.2	31.3	4.5	1.4	32.8	7.8	44.0	3.6	38.3	3.8	50.7	7.4	44.3	6.2	1.4	2.0	4.1	1.76
13	20.7	0.6	1.7	37.7	11.6	0.9	34.7	2.9	1.0	25.7	6.1	1.4	29.7	7.9	34.7	4.2	29.7	0.6	39.7	8.1	34.7	5.0	1.2	1.7	3.9	1.94
14	45.7	3.1	1.8	55.0	18.5	1.5	61.3	3.1	1.4	55.3	4.9	1.5	54.3	6.5	88.3	6.8	73.0	30.3	87.3	6.7	82.9	8.6	1.5	1.9	2.8	0.85
5-FU	100.0	4.4	>167.3	45.7	19.6	>16.1	27.3	10.3	>71.5	17.3	12.2	>60.3	47.6	36.9	>1000	0.0	208.3	72.2	>1000	0.0	>736	457.1	>15.5	>10.0	>32.6

CC₅₀ values refer to the concentrations of the compounds in micromoles which reduce the viable cell number by 50%. Oral squamous cell carcinoma (OSCC) cell lines used are Ca9–22 (derived from gingiva), HSC-2, HSC-3 and HSC-4 (derived from tongue). Normal oral cells used are human gingival fibroblasts (HGF), human periodontal ligament fibroblasts (HPLF) and human pulp cells (HPC). Tumor-specificity (TS) value is calculated by dividing the mean CC₅₀ value of each compound against normal cells by the mean CC₅₀ value against OSCC (D/B or C/A). Selectivity index (SI) figures were generated, which are quotients of the average CC₅₀ values of nonmalignant cells and CC₅₀ figure of a compound toward a specific cell line. A potency selectivity expression (PSE) was calculated by multiplying the reciprocal of average CC₅₀ values toward cancer cell lines and the average SI values toward these cell lines and expressed as a percentage [PSE = (D/B²) × 100]. CC₅₀ value was determined from the growth curves plotted at different concentrations of each compounds in triplicate wells. 5-Fluorouracil (5-FU) were used as a reference drug. Log P values were calculated using ACD/ChemSketch Version 2015 Software. μM : micromolar.

Table 2. Inhibitory effects of sulfonamides 8–14 on hCA I and II isoenzymes.

	IC50 (nM)				Ki (nM)
Compounds	hCA I	r^2	hCA II	r^2	hCA I	hCA II
8	4.81	0.9757	4.95	0.9553	4.84 ± 0.78	4.59 ± 0.83
9	5.29	0.9634	5.63	0.9570	4.59 ± 1.25	7.48 ± 2.52
10	4.84	0.9893	5.37	0.9569	3.99 ± 0.90	5.07 ± 1.69
11	5.68	0.9738	5.72	0.9855	5.10 ± 1.17	4.53 ± 0.75
12	4.91	0.9657	4.25	0.9705	4.49 ± 0.67	4.06 ± 0.60
13	4.22	0.9725	4.65	0.9834	3.73 ± 0.91	4.56 ± 1.08
14	5.13	0.9736	5.45	0.9824	4.17 ± 0.93	3.85 ± 0.57
AZA*	190.12	0.9957	199.62	0.9913	182.93 ± 1.18	194.47 ± 0.34

* Acetazolamide (AZA) was used as a standard inhibitor for both hCA I and II.